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COVID-19 Severity and Thrombo-Inflammatory Response Linked to Ethnicity

ORCID
0000-0002-0348-5934
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Heissig, Beate;
ORCID
0000-0001-6254-6381
Affiliation
An-Najah Center for Cancer and Stem Cell Research, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus 99900800, Palestine
Salama, Yousef;
Affiliation
Department of Internal Medicine II, University Hospital Rechts der Isar, School of Medicine, Technical University, 81675 Munich, Germany
Iakoubov, Roman;
Affiliation
Medical Department II, University Hospital of Frankfurt, 60590 Frankfurt, Germany
Vehreschild, Joerg Janne;
ORCID
0000-0003-1449-4745
Affiliation
Institute of Computing, Federal University of Bahia, Salvador 40110060, Brazil
Rios, Ricardo;
Affiliation
Institute of Computing, Federal University of Bahia, Salvador 40110060, Brazil
Nogueira, Tatiane;
Affiliation
Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany
Vehreschild, Maria J. G. T.;
Affiliation
Department I for Internal Medicine, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany
Stecher, Melanie;
ORCID
0000-0002-7988-5758
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Mori, Hirotake;
Affiliation
Klinikum Passau, 94032 Passau, Germany
Lanznaster, Julia;
ORCID
0000-0002-1623-873X
Affiliation
IMSUT Hospital of The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Adachi, Eisuke;
Affiliation
Department I for Internal Medicine, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany
Jakob, Carolin;
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Tabe, Yoko;
Affiliation
Universitaetsklinikum, 07747 Jena, Germany
Ruethrich, Maria;
Affiliation
Ingolstadt Hospital, 85049 Ingolstadt, Germany
Borgmann, Stefan;
ORCID
0000-0003-1646-9930
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Naito, Toshio;
ORCID
0000-0002-7682-8563
Affiliation
Johannes Wesling Klinikum Minden, Ruhr-Universitaet, 44801 Bochum, Germany
Wille, Kai;
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Valenti, Simon;
ORCID
0000-0001-5967-5238
Affiliation
Klinikum Dortmund gGmbH, Hospital of University Witten/Herdecke, 44137 Dortmund, Germany
Hower, Martin;
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Hattori, Nobutaka;
Affiliation
Universitaetsklinikum, 79106 Freiburg, Germany
Rieg, Siegbert;
ORCID
0000-0003-3578-3351
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Nagaoka, Tetsutaro;
ORCID
0000-0003-1626-4855
Affiliation
Universitaetsklinikum, 40225 Duesseldorf, Germany
Jensen, Bjoern-Erik;
ORCID
0000-0001-7882-5262
Affiliation
IMSUT Hospital of The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Yotsuyanagi, Hiroshi;
Affiliation
Klinikum Bremen-Mitte, 28205 Bremen, Germany
Hertenstein, Bernd;
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Ogawa, Hideoki;
Affiliation
Praxis am Ebertplatz Koeln, 50668 Köln, Germany
Wyen, Christoph;
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Kominami, Eiki;
Affiliation
Internal Medicine III—Gastroenterology and Infectious Diseases, University Hospital of Augsburg, 86156 Augsburg, Germany
Roemmele, Christoph;
Affiliation
IMSUT Hospital of The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Takahashi, Satoshi;
Affiliation
Department of Infectious Diseases and Microbiology, University Hospital Schleswig-Holstein/Campus Luebeck, 23538 Luebeck, Germany
Rupp, Jan;
ORCID
0000-0001-5749-4118
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Takahashi, Kazuhisa;
Affiliation
Emergency Department and Department for Infectious Diseases and Infection Control, University Hospital Regensburg, 93053 Regensburg, Germany
Hanses, Frank;
ORCID
0000-0003-1380-0704
Affiliation
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Hattori, Koichi

Although there is strong evidence that SARS-CoV-2 infection is associated with adverse outcomes in certain ethnic groups, the association of disease severity and risk factors such as comorbidities and biomarkers with racial disparities remains undefined. This retrospective study between March 2020 and February 2021 explores COVID-19 risk factors as predictors for patients’ disease progression through country comparison. Disease severity predictors in Germany and Japan were cardiovascular-associated comorbidities, dementia, and age. We adjusted age, sex, body mass index, and history of cardiovascular disease comorbidity in the country cohorts using a propensity score matching (PSM) technique to reduce the influence of differences in sample size and the surprisingly young, lean Japanese cohort. Analysis of the 170 PSM pairs confirmed that 65.29% of German and 85.29% of Japanese patients were in the uncomplicated phase. More German than Japanese patients were admitted in the complicated and critical phase. Ethnic differences were identified in patients without cardiovascular comorbidities. Japanese patients in the uncomplicated phase presented a suppressed inflammatory response and coagulopathy with hypocoagulation. In contrast, German patients exhibited a hyperactive inflammatory response and coagulopathy with hypercoagulation. These differences were less pronounced in patients in the complicated phase or with cardiovascular diseases. Coagulation/fibrinolysis-associated biomarkers rather than inflammatory-related biomarkers predicted disease severity in patients with cardiovascular comorbidities: platelet counts were associated with severe illness in German patients. In contrast, high D-dimer and fibrinogen levels predicted disease severity in Japanese patients. Our comparative study indicates that ethnicity influences COVID-19-associated biomarker expression linked to the inflammatory and coagulation (thrombo-inflammatory) response. Future studies will be necessary to determine whether these differences contributed to the less severe disease progression observed in Japanese COVID-19 patients compared with those in Germany.

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